Evidence map›Paper›PMID 25925381›Full record

ArticleNeoplasia (New York, N.Y.)2015

Development and validation of a scalable next-generation sequencing system for assessing relevant somatic variants in solid tumors.

Daniel H Hovelson, Andrew S McDaniel, Andi K Cani, Bryan Johnson, Kate Rhodes, Paul D Williams, Santhoshi Bandla, Geoffrey Bien, Paul Choppa, Fiona Hyland and 23 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05372081 (Clinical and Molecular Study With Digital Support of Patients With Inoperable Lung Cancer), which is not on this map. Cited by 132 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 2 pooled it
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05372081 completednot on this mapstarted 2022, after this paper: background citation

Clinical and Molecular Study With Digital Support of Patients With Inoperable Lung Cancer

TypeobservationalSponsorHellenic Cooperative Oncology GroupRan2022 to 2025Enrolled200ConditionsNon-Small Cell Carcinoma of Lung, TNM Stage 4ArmsDigital platform
3 · Its place in the literature

Who cites it

132 citing papers in PubMed, 2 syntheses or guidelines pooled it, 227 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Histopathologic and Molecular Characterization of IDH-Mutant Prostatic Adenocarcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. SJPedPanel: A Pan-Cancer Gene Panel for Childhood Malignancies to Enhance Cancer Monitoring and Early Detection.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

72 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors at 6 institutions in 1 country.

Daniel H HovelsonMichigan Center for Translational Pathology, Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.
Andrew S McDanielDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Andi K CaniDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Bryan JohnsonThermo Fisher Scientific, Ann Arbor, MI, USA.
Kate RhodesThermo Fisher Scientific, Ann Arbor, MI, USA.
Paul D WilliamsThermo Fisher Scientific, Ann Arbor, MI, USA.
Santhoshi BandlaThermo Fisher Scientific, Ann Arbor, MI, USA.
Geoffrey BienThermo Fisher Scientific, Ann Arbor, MI, USA.
Paul ChoppaThermo Fisher Scientific, Ann Arbor, MI, USA.
Fiona HylandThermo Fisher Scientific, Ann Arbor, MI, USA.
Rajesh GottimukkalaThermo Fisher Scientific, Ann Arbor, MI, USA.
Guoying LiuThermo Fisher Scientific, Ann Arbor, MI, USA.
Manimozhi ManivannanThermo Fisher Scientific, Ann Arbor, MI, USA.
Jeoffrey SchagemanThermo Fisher Scientific, Ann Arbor, MI, USA.
Efren Ballesteros-VillagranaThermo Fisher Scientific, Ann Arbor, MI, USA.
Catherine S GrassoDepartment of Pathology, Oregon Health and Sciences University, Portland, OR, USA.
Michael J QuistDepartment of Pathology, Oregon Health and Sciences University, Portland, OR, USA.
Venkata YadatiDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Anmol AminDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Javed SiddiquiDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Bryan L BetzDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Karen E KnudsenDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA; Department of Urology, Thomas Jefferson University, Philadelphia, PA, USA; Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
Kathleen A CooneyDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Felix Y FengDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Michael H RohDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Peter S NelsonDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Chia-Jen LiuDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
David G BeerDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.
Peter WyngaardThermo Fisher Scientific, Ann Arbor, MI, USA.
Arul M ChinnaiyanMichigan Center for Translational Pathology, Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA; Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI, USA.
Seth SadisThermo Fisher Scientific, Ann Arbor, MI, USA.
Daniel R RhodesDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Thermo Fisher Scientific, Ann Arbor, MI, USA.
Scott A TomlinsDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: tomlinss@umich.edu.
Thermo Fisher Scientific (United States) · USUniversity of Michigan–Ann Arbor · USMichigan Center for Translational Pathology · USOregon Health & Science University · USFred Hutch Cancer Center · USThomas Jefferson University · US

Funding

Tissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Timothy Dess · 2014 to 2026
$27.6M
Sequencing, Analysis, and Interpretation of SequencingUM1HG006508 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PIENTA, KENNETH J., ROBERTS, SCOTT · 2013 to 2016
$7.8M
Non Invasive Biomarkers for Diagnosing Clinically Significant Prostate CancerR01CA181605 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NELSON, PETER S · 2014 to 2018
$1.8M
Exploiting drivers of androgen receptor signaling negative prostate cancer for prR01CA183857 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TOMLINS, SCOTT A · 2014 to 2018
$1.6M
SWI/SNF dysregulation in development and diseaseR01CA159945 · NCI · THOMAS JEFFERSON UNIVERSITY · PI KNUDSEN, KAREN E · 2012 to 2016
$1.6M
Identification and Characterization of Gene Fusions in Lung AdenocarcinomaR01CA154365 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BEER, DAVID GEORGE, CHINNAIYAN, ARUL M · 2011 to 2015
$1.4M
NCI NIH HHS P50 CA186786NCI NIH HHS R01 CA154365NCI NIH HHS R01 CA159945NCI NIH HHS R01 CA181605NCI NIH HHS R01 CA183857NHGRI NIH HHS UM1 HG006508
6 · The paper itself

Abstract

Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay [compatible with <20 ng of DNA/RNA from formalin-fixed paraffin-embedded (FFPE) tissues], coupled with an informatics pipeline to specifically identify relevant predefined variants and created a knowledge base of related potential treatments, current practice guidelines, and open clinical trials. We validated OCP using molecular standards and more than 300 FFPE tumor samples, achieving >95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts.

Indexed as

AgedAnaplastic Lymphoma Kinasebeta CateninComputational BiologyDNA Mutational AnalysisDNA, NeoplasmErbB ReceptorsFemaleHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedMutationNeoplasmsProto-Oncogene ProteinsProto-Oncogene Proteins B-rafALK protein, humanAnaplastic Lymphoma Kinasebeta CateninCTNNB1 protein, humanDNA, NeoplasmErbB ReceptorsERG protein, humanKRAS protein, humanProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ras ProteinsReceptor Protein-Tyrosine KinasesSerine EndopeptidasesTMPRSS2 protein, humanTrans-ActivatorsTranscriptional Regulator ERG

Identifiers

PMID25925381
PMCPMC4415141
OpenAlexW2141420424

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.